The transplantation of isolated hepatocytes into affected individuals could be beneficial in the treatment of congenital enzyme deficiencies or hepatocellular degenerative conditions. To investigate such a possibility it is proposed to isolate hepatocytes from heterozygous Gunn rats, radioactively label them in vivo or in vitro and transplant them via the portal vein into the liver of homozygous jaundiced Gunn rats. Pre- and post-operative plasma bilirubin concentrations will be monitored and the liver and other organs of all transplant recipients will be analyzed with light and electron microscope (EM) autoradiography for up to 3 months to obtain both functional and histological evidence of the fate of the transplanted cells and the host responses. Labeled hepatocytes from newborn and developing Gunn rats, adult Wistar rats, adult mice and temporarily maintained cultures of hepatocytes will be similarly transplanted and monitored in homozygous jaundiced Gunn rats to compare the feasibility of performing syngeneic, allogeneic or xenogeneic transplantation of hepatocytes. Transplantation of isolated, labeled, rabbit hepatocytes via the mesenteric or umbilical veins, respectively, will be investigated to determine the potentialities of these transplantation routes as alternatives to direct intraportal infusion, in larger animals and man.